PROJECT SUMMARY Osteoarthritis (OA) is a degenerative joint disease, affecting more than 27 million people in the United States alone. By 2030 approximately 67 million people will be affected by OA. This large affected population and the severe consequent debility of OA lead to significant expenses to the health care system. OA is characterized by biochemical, structural and morphologic degradation of components of the extracellular matrix (ECM) of articular cartilage. The ECM is composed of primarily two groups of macromolecules including proteoglycan (PG) and collagen fibers. Early diagnosis of cartilage degeneration would require the ability to non-invasively detect changes in PG concentration and collagen integrity before morphological changes occur. T1? and T2 relaxation times are affected by these pathological processes and are the most widely used biochemical cartilage MRI sequences worldwide. Several researchers have demonstrated that the T1? relaxation time is more sensitive to proteoglycan content of the cartilage, while T2 relaxation time is more sensitive to collagen orientation and integrity of network and hydration. These imaging biomarkers have potential to detect early stages of the disease (pre-clinical), quantitatively assess disease severity, monitor disease progression and possibly monitor OA therapy. The overarching goal of this proposal is to develop, evaluate and translate highly accelerated 3D-T1? and T2 mapping (each protocol under 5 minutes) for in-vivo knee OA applications on a standard clinical 3T scanner employing novel compressed sensing (CS) and parallel imaging (PI) strategies. The proposed accelerated 3D- T1? and T2 mapping techniques can be easily incorporated into routine clinical protocols for biochemical assessment of cartilage in addition to standard morphological evaluation and could serve as future imaging biomarkers for disease modifying therapies for OA. The outcome of this proposed study will significantly impact our ability for personalized treatment regimens and possibly prevent the development of premature OA. Finally, we intend on disseminating the sequences to other academic sites for widespread implementation and future multicenter studies.